Demographic and clinical characteristics of patients and their responses to treatment with SP and CQ.

<p>ACPR = Adequate Clinical and Parasitological Response; TF = Treatment failure, ETF = Early Treatment Failure, LCF = Late Clinical Failure; LPF = Late Parasitological Failure; CF = Clinical failure, TF = Treatment failure.</p><p>Demographic and clinical characteristics of patients and their responses to treatment with SP and CQ.</p

Map of the studied areas of north east India.

<p>Map of the studied areas of north east India.</p

Age and codon wise association of CQ (above) and SP (below) ETF.

<p>Age and codon wise association of CQ (above) and SP (below) ETF.</p

Frequency of allelic combinations mostly conferring resistance to SP.

<p>Frequency of allelic combinations mostly conferring resistance to SP.</p

Sample size, site and genotyped codon wise.

<p>Sample size, site and genotyped codon wise.</p

The frequency distribution of SNPs combination for <i>dhps</i> alleles.

<p>Allelic combinations are in order of S436F/A, A437G, K540E, A581G, and A613S/T, where bold and underlined alleles denotes mutations. Values within bracket are the percentage of occurrences.</p><p>The frequency distribution of SNPs combination for <i>dhps</i> alleles.</p

<i>dhps/dhfr</i> haplotypes associated with CQ and SP early treatment failure (ETF).

<p>Allelic combinations are in order of S436F/A, A437G, K540E, A581G, and A613S/T (<i>dhps</i>)-A16V, C50R N51I, C59R, S108N and I164L (<i>dhfr</i>) where bold alleles denotes mutations.</p><p><i>dhps/dhfr</i> haplotypes associated with CQ and SP early treatment failure (ETF).</p

Prevalence of <i>dhps</i> and <i>dhfr</i> mutations in isolates of <i>Plasmodium falciparum</i>.

<p>Values within bracket are the percentage of occurrences.</p><p>Prevalence of <i>dhps</i> and <i>dhfr</i> mutations in isolates of <i>Plasmodium falciparum</i>.</p

Prevalence of <i>dhps</i> and <i>dhfr</i> point mutations in the study.

<p>Prevalence of <i>dhps</i> and <i>dhfr</i> point mutations in the study.</p

Molecular Evidence of Increased Resistance to Anti-Folate Drugs in <i>Plasmodium falciparum</i> in North-East India: A Signal for Potential Failure of Artemisinin Plus Sulphadoxine-Pyrimethamine Combination Therapy

<div><p>North-east India, being a corridor to South-east Asia, is believed to play an important role in transmitting drug resistant <i>Plasmodium falciparum</i> malaria to India and South Asia. North-east India was the first place in India to record the emergence of drug resistance to chloroquine as well as sulphadoxine/pyrimethamine. Presently chloroquine resistance is widespread all over the North-east India and resistance to other anti-malarials is increasing. In this study both <i>in vivo</i> therapeutic efficacy and molecular assays were used to screen the spectrum of drug resistance to chloroquine and sulphadoxine/pyrimethamine in the circulating <i>P. falciparum</i> strains. A total of 220 <i>P. falciparum</i> positives subjects were enrolled in the study for therapeutic assessment of chloroquine and sulphadoxine/pyrimethamine and assessment of point mutations conferring resistances to these drugs were carried out by genotyping the isolates following standard methods. Overall clinical failures in sulphadoxine/pyrimethamine and chloroquine were found 12.6 and 69.5% respectively, while overall treatment failures recorded were 13.7 and 81.5% in the two arms. Nearly all (99.0%) the isolates had mutant <i>pfcrt</i> genotype (76T), while 68% had mutant <i>pfmdr</i>-1 genotype (86Y). Mutation in <i>dhps</i> 437 codon was the most prevalent one while <i>dhfr</i> codon 108 showed 100% mutation. A total of 23 unique haplotypes at the <i>dhps</i> locus and 7 at <i>dhfr</i> locus were found while <i>dhps</i>-<i>dhfr</i> combined loci revealed 49 unique haplotypes. Prevalence of double, triple and quadruple mutations were common while 1 haplotype was found with all five mutated codons (<b><u>F/AGEGS/T</u></b>) at <i>dhps</i> locus. Detection of quadruple mutants (51I/59R/108N/164L) in the present study, earlier recorded from Car Nicobar Island, India only, indicates the presence of high levels of resistance to sulphadoxine/pyrimethamine in north-east India. Associations between resistant haplotypes and the clinical outcomes and emerging resistance in sulphadoxine/pyrimethamine in relation to the efficacy of the currently used artemisinin combination therapy are discussed.</p></div